The cell can be regarded as the true framework for the structural and functional organization of living matter. A functional description of the living cell must take into consideration a dynamic structure with vast synthesizing capacities, self-duplicating properties and far- reaching interactions with the environment. We are as yet ignorant as to the molecular mechanisms whereby the cell regulates the multitude of its reactions, yet a state of equilibrium must be achieved. Deviation from homeostasis results in molecular disease. The present problem concerns the molecular mechanisms operative in regulation of isoleucine- valine synthesis. Amino acid analogues have been used as probes to identify regulatory elements for the pathway in Bacillus subtilis. One class of analogue resistant mutants, which synthesizes elevated levels of biosynthetic enzymes under conditions of repression has been shown to have a modified isoleucyl tRNA synthetase. Wild type and mutant synthetases will be purified in order to relate the structure of the enzyme to its role in cell metabolism. Additional analogue resistant mutants which have derepressed levels of biosynthetic enzymes will be characterized genetically and biochemically. The factors which regulate the flow of carbon through the pathway will be examined in terms of the enzymology and feedback control of the first enzyme specific to valine biosynthesis.